title: Glomerulopathy in spontaneously obese rhesus monkeys with type 2 diabetes: a stereological study.
abstract: BACKGROUND
  Animal models could provide insights into the diabetic nephropathy pathogenesis; however, available rodent models do not mirror the heterogeneity of lesions in type 2 diabetic patients, and do not progress to end-stage renal disease. Previous studies showed that spontaneously obese type 2 diabetic rhesus monkeys develop many of the features of human diabetic glomerulopathy, and may progress to end-stage renal disease. Here, in order to further characterize diabetic glomerulopathy in this model, we used electron microscopic stereology.
  
  
  METHODS
  Renal biopsies from 17 diabetic, 17 pre-diabetic/metabolic syndrome and 11 non-diabetic monkeys were studied. Fractional volumes of mesangium [Vv(Mes/glom)], mesangial matrix [Vv(MM/glom)] and mesangial cells [Vv(MC/glom)], glomerular basement membrane width and peripheral glomerular basement membrane surface density per glomerulus [Sv(PGBM/glom)] were estimated. Glomerular filtration and albumin excretion rates were measured in a limited number of animals. Glomerular structural and biochemical/metabolic data were compared among the groups.
  
  
  RESULTS
  Compared to non-diabetic monkeys, diabetic rhesus monkeys showed classic diabetic nephropathy changes, including glomerular basement membrane thickening (p = 0.001), increased fractional volumes of mesangium (p = 0.02), and reduced peripheral glomerular basement membrane surface density per glomerulus (p = 0.03) compared to non-diabetic monkeys. Increased fractional volumes of mesangium was primarily due to increased mesangial matrix (p = 0.03). Glomerular structural parameter inter-relationships in diabetic monkeys mirrored those of human diabetic glomerulopathy. Albumin excretion rate was greater (p = 0.03) in diabetic vs. non-diabetic monkeys. There was trend for a positive correlation between albumin excretion rate and fractional volumes of mesangium.
  
  
  CONCLUSIONS
  This rhesus primate model shares many features of human diabetic glomerulopathy. Mesangial expansion in this model, similar to human diabetic nephropathy and different from available rodent models of the disease, is primarily due to increased mesangial matrix.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA. najafian@uw.edu
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.forename: Awais
authors.initials: A
authors.lastname: Masood
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Malloy
authors.forename: Alfonso
authors.initials: A
authors.lastname: Campos
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Hansen
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
authors.forename: M Luiza
authors.initials: ML
authors.lastname: Caramori
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000648:ultrastructure; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000648:ultrastructure; D007668:Kidney / Q000503:physiopathology / Q000648:ultrastructure*; D008253:Macaca mulatta; D024821:Metabolic Syndrome / Q000150:complications; D009765:Obesity / Q000150:complications*; D011236:Prediabetic State / Q000150:complications; D012720:Severity of Illness Index